Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Ageing Res Rev. 2023 Jul;88:101951. doi: 10.1016/j.arr.2023.101951. Epub 2023 May 8.
Organelles form tight connections through membrane contact sites, thereby cooperating to regulate homeostasis and cell function. Among them, the contact between endoplasmic reticulum (ER), the main intracellular calcium storage organelles, and mitochondria has been recognized for decades, and its main roles in the ion and lipid transport, ROS signaling, membrane dynamic changes and cellular metabolism are basically determined. At present, many tumor chemotherapeutic drugs rely on ER-mitochondrial calcium signal to function, but the mechanism of targeting resident molecules at the mitochondria-associated endoplasmic reticulum membranes (MAM) to sensitize traditional chemotherapy and the new tumor therapeutic targets identified based on the signal pathways on the MAM have not been thoroughly discussed. In this review, we highlight the key roles of various signaling pathways at the ER-mitochondria contact site in tumorigenesis and focus on novel anticancer therapy strategies targeting potential targets at this contact site.
细胞器通过膜接触位点形成紧密连接，从而协同调节细胞内稳态和功能。其中，内质网（ER）与线粒体之间的接触已被认识了几十年，其在离子和脂质运输、ROS 信号转导、膜动态变化和细胞代谢中的主要作用基本已确定。目前，许多肿瘤化疗药物依赖于 ER-线粒体钙信号发挥作用，但针对驻留于线粒体相关内质网膜（MAM）上的分子的靶向治疗以及基于 MAM 上信号通路的新的肿瘤治疗靶点的机制尚未被深入探讨。在这篇综述中，我们强调了 ER-线粒体接触部位各种信号通路在肿瘤发生中的关键作用，并重点关注针对该接触部位潜在靶点的新型抗癌治疗策略。
